Gail D. Burd - US grants

This proposal requests funds for the purchase of a computer- aided system for the reconstruction, measurement and statistical analysis of neuronal processes from sectioned or whole-mounted nervous tissue. The central goal of all the projects described is to understand how the detailed structure of neurons and their anatomical relationship?s with one another translate into the precise functioning of the nervous system. Five of the major users have projects that utilize various aspects of the insect nervous system as test subjects, a sixth investigates neural development in the amphibian nervous system.

Development of the central nervous system is dependent upon precisely- timed cellular and molecular interactions between specific neural elements. If these interactions fail to take place, as in the case of birth defects or embryonic neurological disorders, a cascade of irreversible developmental problems may ensue. The thrust of this proposal is to examine cellular interactions in a brain region that is critically-dependent upon timely development of innervation by sensory afferent axons for its growth and maturation. Thus, in the African clawed frog, Xenopus laevis, we will continue our examination of the development of the olfactory bulb with particular reference to examining the effects of sensory deafferentation on the development of the olfactory bulb, including determination of the fate of differentiated mitral/tufted cells (output neurons of the bulb), volume of the bulb, number of mitral/tufted cells, and neurogenesis. We will also examine the influence of supernumerary peripheral olfactory tissue on the volume of the bulb and the number of output neurons, and the expression of developmentally-regulated genes in the olfactory bulb. We will study these issues by experimentally-manipulating the peripheral innervation through the removal of nasal capsules at different stages of development or transplantation of an extra nasal capsule so that it will innervate the olfactory bulb during early stages of larval development. Experimental approaches will make use of light and electron microscopy, cell birthdating, neuroanatomical tract-tracing, in situ hybridization, and various techniques of molecular biology. The underlying purpose of these experiments is to identify the cellular and molecular elements that are induced or controlled by sensory afferents during critical periods of development, with the ultimate goal of identifying the factors in afferent fibers that perform these functions.

9306848 Burd This Career Advancement Award for Women provides partial support for a sabbatical leave. The goal of the study is to examine cell lineage of and differential gene expression in the olfactory placodes of the frog, Xenopus laevis. Cell lineage experiments consist of injecting dyes into cells in the anterior neural plate, and following the migration of injected cells with a SIT camera and time-lapsed video recordings. Likewise, the source of cells in regenerating olfactory placodes will be determined. Two genes (distal-less and empty spiracles) known to be expressed in mouse olfactory placodes will be characterized in Xenopus placodes. The pattern of expression of these genes will be determined with in situ hybridization and Northern blots. This study will determine factors that regulate differentiation and regeneration of the olfactory placodes. Development of a fertilized egg into a multicellular organism is controlled by an array of genes and tissue interactions that determine the fates of particular cell and tissue types. The goal of this study is to examine developmental expression of genes and the formation and regeneration of the peripheral tissue for the sense of smell, the olfactory epithelium, in the frog. Fluorescent dyes will be injected into cells that are thought to form or reform the olfactory placode, the precursor tissue to the olfactory epithelium. The long-term goal of this study is to determine the molecular and cellular factors that regulate development and regeneration in the developing nervous system, using the peripheral olfactory system as a model. ***

DESCRIPTION (Adapted from applicant's abstract) Thyroid hormone plays a crucial role in the development of the nervous system by inducing a variety of anatomical, physiological, biochemical, and molecular events during critical periods. One in every 40000 newborns have congenital hypothyroidism that will lead to growth deficiencies and irreversible mental retardation unless thyroid hormone treatment begins within the first four weeks of life. In addition hypothyroidism results in several neurological disorders in adults, including reduction or loss of olfactory abilities. The thrust of this proposal is to determine the influence of thyroid hormone on the development of the olfactory system using a model system-the olfactory epithelium of the clawed frog, Xenopus laevis. Adult Xenopus have a tripartite olfactory system that consists of olfactory epithelium in the principal and middle cavities and vomeronasal epithelium in the vomeronasal organ. Different classes of odorant receptor genes have been isolated from the adult principal cavity and middle cavity that resemble mammalian and fish odorant receptor genes respectively. The adult olfactory structures are formed at metamorphosis when the middle cavity develops de novo and the principal cavity undergoes radical cellular and biochemical transformations. The specific aims of the current proposal are to: (1) determine whether thyroid hormone is required for development of the middle cavity, (2)determine whether all the receptor cells in the principal cavity die and are replaced at metamorphosis, (3) determine the temporal and spatial expression patterns of mammalian-like and fish-like odorant receptor genes, and (4) determine whether thyroid hormone levels influence the cellular changes and odorant receptor gene expression patterns in the developing olfactory epithelium. These goals will be accomplished with hormonal manipulations, immunocytochemistry, electron microscopy, neuronal tract tracing, RT-PCR, and in situ hybridization. The goal of this research is to provide insight into thyroid hormone regulation of olfactory system development using an experimentally-favorable model system.

This project is a partnership among the science and mathematics disciplines in the College of Science. The goals are to enhance appreciation for the integration of scientific disciplines, to improve academic performance and university graduation in the sciences, and to prepare undergraduates to enter the science and technology workforce or graduate school.

Intellectual Merit: Scholars begin the program as sophomores or juniors, have high academic potential and financial need, and are selected from the disciplines of astronomy, biological sciences, chemistry, computer science, geosciences, mathematics, and physics. The program features enrichment activities designed to make scholarship recipients successful in college and prepared for the workforce or graduate school. The activities include a faculty and peer mentor, lectures by and informal meetings with interdisciplinary scientists, opportunities to do independent research or a scientific internship with a scientist or mathematician, a course in integrated science, travel to scientific meetings, and a Graduate Record Exam (GRE) workshop.

Broader Impacts: Underrepresented groups are being recruited using minority organizations on campus. Assessment includes formative and summative evaluations. One study compares scholarship recipients and students with similar academic characteristics by looking at graduation rates in the supported disciplines and the number of students who enter graduate school or the science/technology workforce. In addition, the program includes opportunities for scholarship recipients to do hands-on science and math activities through the Science Connection program in elementary or middle schools that have a high percentage of minority students.

Interdisciplinary (99)
The overarching goal of this project is to provide undergraduate students with interdisciplinary skills that will help them remain abreast of and understand the content and organization of rapidly growing scientific knowledge. This goal is being addressed by developing a laboratory course for sophomores majoring in any of the natural science disciplines. The course consists of four student-centered, inquiry-based modules - each of which cuts across multiple disciplines, namely, (1) protein folding, (2) biological motion, (3) physical phenomena at multiple scales, and (4) entropy. The impact of this approach on student learning is being assessed and will be published in science education journals. An online laboratory manual is being prepared.

Intellectual Merit: The effectiveness of future STEM professionals depends in part on their skill in integrating knowledge across disciplines, often in teams. This project is designing activities that provide students with broad experiences in solving complex problems in interdisciplinary settings. The laboratory course is designed as a complement to the typical series of discipline-based courses offered by traditional departments in the natural sciences and mathematics. It is also a core requirement for a new major in Integrated Science.

Broader Impacts: This course is building on integrated science courses at Princeton University and Harvey Mudd College. It is closely modeled on the Harvey Mudd design. Future collaborative work is planned to design and assess integrated science laboratory courses for students from different backgrounds and levels of scientific preparation at other colleges and universities.

This project will significantly improve opportunities for learning experienced by all students in large enrollment introductory STEM courses. Too often, undergraduate introductory STEM courses are offered in 100+ seat lecture halls where student engagement in the hard work of learning new information, as opposed to simply listening to an expert talk about it, is the exception rather than the rule. Many undergraduates entering STEM majors need help in learning how to learn, especially in large enrollment classes with challenging STEM content. This project will change this situation. Using large classrooms recently redesigned for small group collaborations, this project will use evidence from research on learning, teaching, and assessment to create and refine a model for training teams of STEM instructors and their instructional assistants as learning leaders. All students in the collaborative learning environments, with guidance and support from the instructional team, will have opportunities to learn STEM in collaborative, task-oriented classes. Simultaneously, students will learn how to learn STEM in an environment which likely resembles the work environment of their future professional careers.

This project will generate a professional development model that improves instructional team members' abilities to practice evidence-based instruction in large enrollment undergraduate STEM collaborative learning environments (CLEs). The quality of instruction and assessment practiced by these teams is an important aspect of successful student learning in large enrollment CLEs. Each team will be comprised of four roles: (1) a lead instructor, a faculty member who will be the primary instructor, curriculum planner, and developer of learning tasks; (2) a learning assistant trainer, a faculty member who will train learning assistants on evidence-based practices for engaged student learning; (3) assessment coaches, experienced learning assistants who will serve as lead assessors of student engagement by monitoring and supporting learning coaches' formative assessment practices and feedback providers to lead instructors and learning assistant trainers; (4) learning coaches, learning assistants who will directly engage with students and provide formative assessment. The project will build upon research on learning task quality, formative assessment practices, and student-assisted teaching, which suggests that productive student learning in large enrollment CLEs: (1) requires engagement with appropriately challenging, high quality learning tasks, (2) is fostered with evidence-based formative assessment practices, and (3) involves efficient functioning of instructional teams prepared to support student learning with evidence-based practices. Built upon these premises, the project's professional development activities will build instructional team members' abilities to succeed in their roles. Research goals are to: (1) track changes in task quality, formative assessment practices, and instructional team performance over several semesters within six to nine large enrollment CLEs, and (2) document and describe the challenges associated with achieving the desired evidence-based practices of task development, formative assessment, and instructional team performance using, and annually revising, the professional development model.